Biomolecular Electronics. Bioelectronics and the Electrical Control of Biological Systems and Reactions

241 Pages·2014·7.549 MB·English

by  Paolo Facci (Auth.)

Biomolecular Electronics
Bioelectronics and the Electrical
Control of Biological Systems
and Reactions
Paolo Facci
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Preface
At the beginning of the 1990s biomolecular electronics asserted itself as
a powerful novel approach to combine the most advanced technology
humankind has ever developed with the most sophisticated type of matter
knownintheUniverse,biologicalmatter.Expressionssuchasself-assembly,
specific recognition, natural evolution, and so on, suddenly became very
popularandwidelyused(andsometimes,abused),includingbypeoplelack-
ing a rigorous biological education.
I think that words (and the concepts that these words signify) do not
belong to anyone in particular and everybody has the right to use them at
will.Sometimes,thiscanturnouttobealittleannoyingforeducatedpeople
but more often, especially in science, it helps to provide an undeniably
advantageous change of paradigm that can foster cultural advancement.
Apparently something similar has happened also in the development of
biomolecular electronics. Cross-contamination among basic and applied
disciplines helped a lot to shape the brand new research field that aimed at
selecting and exploiting molecules of biological origin for implementing
novel hybrid devices. These last were characterized by a novel concept
according to which the molecule itself constituted the device, at variance
with the classical top-down approach borrowed from fabrication processes
used in solid-state electronics.
In this regard, the concomitant advent of nanotechnology resulted in
a powerful boost for biomolecular electronics, which naturally faced the
issue of connecting electronic circuits and leads to single molecules.
Aftermorethan20yearsfromitsbirthonemustadmit,however,thatreal
practicalbiomolecularelectronicsapplications,intermsofoperatingdevices
on the market, are still dramatically missing and the legitimate doubt arises
that they will never appear!
This outcome is indeed quite common in applied science and often
accompanies those cases that were characterized by a generalized over-
excitement about their expectations. To date, not many experts trust in the
future advent of transistors made from proteins or DNA.
At any rate the positive side-products, brought about by more than two
decadesofresearchinthisfield,arenumerousandrangefromadeepunder-
standingofelectrontransportthroughsinglebiomolecules,totheelucidation
ofthekeyroleofcontactswithmetalleadsandthatofredoxelectroniclevels
in assisting electron transport, to the correct appreciation of conformational
variationsinmodulatingmoleculartransportproperties.Theessentialroleof
XV
XVI Preface
water in enabling and preserving functional molecular conformations has
once more been clarified.
Iwouldlistinthepositiveoutcomesoftheresearchactivityinbiomolec-
ularelectronicsalsotherealizationthatitstrueaddedvalueisnotlikelytobe
in competing with much better-established technological paradigms to
replacealreadyexistingandwellperformingdevices(e.g.,nanotransistors);
rather, it is in having developed a series of approaches suitable for the
effectiveinterfacingofbiologicalmoleculesandreactionswithconventional
electronic systems.
Indeed,thisfactenableselectroniccontroloverthefunctionalactivityof
biologicalmolecules(e.g.,metalloenzymes)andrelatedreactionsandpaves
thewaytoafuturescenariowherebiologicalphenomenaandsystemswillbe
controllableanddriventechnologicallybyexternalelectricsignals.Thefirst
stepstowardsthisnovel,charmingscientificandtechnologicaladventureare
what the present book is about.
DuringmyactivityinthefieldofbiomolecularelectronicsIhavehadthe
opportunity of sharing with numerous young collaborators, students, and
colleagues many ideas, efforts, lack of success, and, sometimes, also the
happiness of exalting results. I am grateful to all of them. In particular,
IthankAndreaAlessandrini,VictorErokhin,GerardCanters,LorenzoBerti,
Marco Salerno, Dario Alliata, Laura Andolfi, Carlo Augusto Bortolotti,
Mimmo Gerunda, Paolo Petrangolini, Marialuisa Caiazzo, Elena Angeli,
and Loredana Longo, who more than others have collaborated with me in
this field and without whom I could not have reached the present view of
this subject.
Paolo Facci, Genova
CHAPTER
1
Biomolecular Electronics
CHAPTER OUTLINE
1.0 What is biomolecular electronics?...........................................................1
1.1 Proteins andbiomolecular electronics......................................................3
1.2 Proteins andplanardevices.....................................................................6
1.3 The future of biomolecularelectronics...................................................10
1.4 A novel idea: electrical control ofbiomolecular systems.........................12
1.5 References............................................................................................15
1.0 What is biomolecular electronics?
With the expression “biomolecular electronics” we refer nowadays to that
branchoftechnologythatexploitsmoleculesormolecularsystemsofbiolog-
ical origin for interaction with modern electronics.
The idea of using biomolecules to assemble hybrid electronic devices
stems from molecular electronics (Aviram & Ratner, 1974) and, as such, is
intimatelyconnectedwiththeadventofnanosciencesandnanotechnologies,
datingbacktothebeginningofthelastdecadeofthepastcentury.Theinter-
est in biomolecules stems not only from their size, which is typically in the
nanometerrange(atleastintwospatialdimensions).Rather,itisoftencon-
nected to a particular standpoint from which one can regard them.
Indeed, an interesting point of view is that of regarding biomolecules in
general and proteins in particular as self-contained, nanometer-sized func-
tional units that are highly specialized and efficient in performing a certain
functional task. Their efficiency in performing a particular activity is traced
backtothefactthatbiomolecules,beingpartsoflivingbeings,havenaturally
evolved over billions of years, reaching the current “optimal” degree of
specialization for accomplishing a given task.
Onecanoftencomeacrossthisopinionreadingthespecializedliterature
or attending topical conferences; however, it appears quite questionable in
lightofaslightlylessna¨ıveunderstandingoftheTheoryofEvolution(Fodor
&Piattelli-Palmarini,2010);nevertheless,itisperhapsagoodenoughstart-
ing point to understand the historical motivations which led to the
1
BiomolecularElectronics.http://dx.doi.org/10.1016/B978-1-4557-3142-8.00001-7
Copyright©2014ElsevierInc.Allrightsreserved.
2 CHAPTER 1 Biomolecular electronics
remarkableinterestshownbyasizablepartoftheinterdisciplinaryscientific
community in the use of biomolecules for assembling electronic devices.
Another element motivating the interest in proteins as components of
electronic circuits is their sizes. Indeed, these molecules often configure
self-consistent, functional units with typical sizes in the nanometer range.
Therefore,itisconceivabletoimaginefunctionaldevicesassmallasasingle
molecule, especially in view of the fantastic progresses in miniaturization
and parallelization made with nano-lithographic techniques.
Furthermore, the rich chemistry that particularly characterizes protein-
forming monomers, i.e., the 20 natural amino acids, makes these molecules
amenabletovariouskindsofchemicalfunctionalization,thusimprovingtheir
reactivitytowardsdesiredfunctionalgroupsandenabling,asaconsequence,
their ready chemisorption on pre-functionalized structures and surfaces.
Moreover, the exceptionally fine-tuned recognition properties of biological
structures(e.g.,complementarynucleicacidstrands,DNA-bindingproteins,
antibody-antigen or receptor-ligand pairs, etc.) could allow for self-
assembling of more complex structures in the nanometer-sized gap between
meso/nanoscale electrodes.
Among the various classes of molecules of biological origin, two of
them have been especially focused upon by researchers in the field:
DNA and proteins. The reasons for this choice are different; in the case
of DNA, its robustness and ease of handling are relevant factors. Neverthe-
less, a further important aspect fostering DNA as an interesting molecule
in biomolecular electronics stemmed from the idea that, if we could under-
stand the mechanism by which electrons are driven along the double helix
during DNA repair of damage caused by oxidative stress, wewould obtain,
as a byproduct, a way to produce molecular wires, that is, one-molecule-
thick conducting wires, to be used in assembling (bio)molecular circuitry.
If DNA can be regarded in terms of molecular wire, what else does one
need to assemble molecular circuits? Some functionally relevant electronic
elements, of course. Those were identified as the proteins, which are
indeed deputed to perform the main functional tasks in the organisms
that express them.
At this point a relevant question arose that has not been completely
answeredyet, about the electrical conductivity of biomolecules.It is indeed
obviousthatatthebasisofanyelectroniccircuitthereisaneedtodealwith
wiresandelementsthatcanconductor,moregenerally,interactfunctionally
with electron flows, i.e., electron currents.
Whereasthisissueis stillopeninthecase of DNA,whichdisplaysgood
conductivityovershortranges(oftheorderofnanometers)andappearstobe
1.1 Proteins and biomolecular electronics 3
an insulator over larger distances (Guo et al., 2008), the situation regarding
proteinsismorecomplexandrequiresdetailedanalysisbecauseofthelarge
variabilityoftheirproperties(mirroringthedifferencesinproteinstructures).
In the case of DNA, its poor conductivity, at least in the mesoscopic
range, has prompted various approaches for enhancing it, based on doping
(with metal ions or intercalating agents (Ban et al., 2009)) or on the use of
DNA as a molecular template for metal nanowire growth (Berti et al.,
2005).Inthecaseofproteins,whichpossessanintrinsicallyhigherchemical
and structural variability compared with DNA, it is not surprising that spe-
cific transport proteins, carrying either electrons or ions, soon attracted the
interest of researchers.
1.1 Proteins and biomolecular electronics
Typically, electron transport proteins are water-soluble molecules (rare ex-
ceptions apart; see, e.g., cytochrome b , a transmembrane three-heme
561
cytochrome), whereas ion transport proteins are membrane molecules
requiringspecificenvironmentalconditions(incorporationinalipidbilayer)
to be functionally active (see section 3.6.1). According to this difference,
whereas the former are more easily implemented in electronic circuits, the
latter are more demanding to exploit in a nano-circuit configuration. Ion
channelshavebeenusedto gatetransistorsin hybriddevicesthanksto their
selectivityforspecificions(Bernardsetal.,2006)andtheinherentsimilarity
of thegating mechanism of voltage-gated ion channels to the basic features
of a field-effect transistor (Bezanilla, 2005). A specific application of ion
channels in electronic circuits for sensing applications is the coupling of
the channels reconstituted in lipid bilayers with other electronic nanostruc-
tures such as semiconductor nanowires (Misra et al., 2009). Examples of
these applications are the possibility, by changing the pH of the solution,
of controlling the conductance of a silicon nanowire covered with a lipid
bilayerintegrating peptidepores and thecreation of nanobioelectronictran-
þ þ
sistors exploiting ion pumps such as Na /K -ATPase (Huang et al., 2010).
However,themostpopularandcharmingclassofproteinsthatseemedto
beparticularlysuitableforimplementingelectronicdevicesistheredoxmet-
alloproteins.Theseveryimportantmoleculesareindeedabletoshuttleelec-
tronsbetween molecularpartnersbyreversibly changingthe oxidationstate
of the metal ions they contain (see sections 4.1, 4.1.1, and 4.1.2).
Following the route defined by conventional solid-state electronics, the
research efforts in biomolecular electronics have generally focused on
4 CHAPTER 1 Biomolecular electronics
demonstratingtransistor-likebehaviorthatproteinsmightdisplaywhenposi-
tionedbetweentwoelectrodes.However,consideringtheclassicdefinitionof
a transistor,we should stress here a different meaning for the sameword. A
transistor represents a device composed of at least three electrodes (source,
drain,andgate)whichisabletoamplifyorswitchthecurrentbetweenapair
of electrodes (e.g., source-drain) by controlling the voltage or current be-
tweentwoofthesethreeelectrodes(e.g.,source-gateordrain-gate).Incon-
ventionalelectronicsthecontrollingsignalisanelectricsignal.Inthecontext
ofproteins,amongthepossiblesignalsthatcanfunctionforgatinga hybrid
deviceweincludealsoothersignalsofachemicalorphysicalnature.Among
them one has to consider all the parameters that are able to modify, at con-
stant bias voltage, the transport properties of a protein or of a protein layer
sandwiched between two electrodes. In a similar way, protein conforma-
tional variations can induce changes in its transport properties or in those
of another nanostructure to which the protein is coupled. Among these sig-
nalsonecanlistvariationinenvironmentalpH,temperature,substraterecog-
nition by enzymes and so on. The sensitivity to any of these signals confers
sensing properties to the related devices.
We will consider the main results obtained along the pathway of un-
derstanding the behavior of redox metalloproteins when used as active
parts of hybrid electronic devices in Chapter 4. Here, we continue by
noting that other features of proteins have also attracted researchers’
attention and have been used in various attempts to exploit the properties
of natural biomolecules to implement electronic devices. There is, for
instance, the case of antibodies. These molecules are part of an organ-
ism’s immune system and are known for their specific recognition and
binding capabilities against the corresponding antigens. Their use has
been recently demonstrated in assembling single-protein devices (Chen
etal.,2012).Particularly,antibodiesoftheIgGtype(immunogammaglobu-
lin) have been raised against Au nanoparticles, 5 nm in diameter. An IgG
molecule can bind up to two of these gold nanoparticles, one per F frag-
ab
ment,wherethespecificrecognitionsitesforantigensarelocated.Thisspe-
cific binding provides a stable bond. Gold nanoparticles are attached to
e-beam lithography-fabricated 10-nm gap electrodes that act as source
and drain electrodes. Once the electrodes have been decorated with nano-
particles,they are exposed to IgGs that specifically recognize the nanopar-
ticles,bindingthemfirmly.Thisresultsinaconfigurationthatcanbegated
electrically, by means of a proximal electrode, and optically, by the action
ofaCdSeQdotattachedtotheIgGmoleculeatitsF fragment.Whileirra-
c
diated, the Qdot absorbs light, providing an induced dipole moment